The objective of this investigation is to use chemical cross-linking reactions and chemical modification together with mass spectrometric techniques to study the contact interactions between protein-protein and protein-DNA complexes. Various cross-linking and modification reagents have been selected for these investigations. Reagents that probe the accessibilities of a number of amino acid side-chains have been investigated, including His, Try, Lys, and Arg. Our studies have shown that laser desorption MS is very useful in following the nature and extent of reaction. We are currently developing the use of the MALDI-Ion Trap to map the sites of modifications with CAD-MS/MS.